Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive aging. Young cells possessed highly diverse circular DNA populations but 94% of the circular DNA were lost after ∼15 divisions, whereas rDNA circles underwent massive accumulation to >95% of circular DNA. Circles present in both young and old cells were characterized by replication origins including circles from unique regions of the genome and repetitive regions: rDNA and telomeric Y’ regions. We further observed that circles can have flexible inheritance patterns: [HXT6/7^circle] normally segregates to mother cells but in low glucose is present in up to 50% of cells, the majority of which must have inherited this circle from their mother. Interestingly, [HXT6/7^circle] cells are eventually replaced by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNAs are intermediates in chromosomal amplifications. In conclusion, the heterogeneity of circular DNA offers flexibility in adaptation, but this heterogeneity is remarkably diminished with age.

中文翻译：

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复制衰老与酿酒酵母染色体外环状 DNA 遗传异质性的丧失有关。


环状DNA可以产生于真核染色体的所有部分。在酵母中，环状核糖体 DNA (rDNA) 随着细胞衰老而急剧积累，然而，人们对其他染色体衍生环的积累或此类环对衰老细胞遗传变异的贡献知之甚少。我们对年轻时和长期老化后采样的酿酒酵母群体中的环状 DNA 进行了分析。年轻细胞拥有高度多样化的环状 DNA 群体，但 94% 的环状 DNA 在~15 次分裂后丢失，而 rDNA 环经历了大量积累，达到 >95% 的环状 DNA。年轻和年老细胞中存在的环的特征在于复制起点，包括来自基因组的独特区域和重复区域的环：rDNA和端粒Y'区域。我们进一步观察到，环可以具有灵活的遗传模式：[ HXT6/7^环]通常分离到母细胞，但在低葡萄糖情况下存在于高达 50% 的细胞中，其中大多数必须从母细胞遗传了这个环。有趣的是，[ HXT6/7^环]细胞最终被携带稳定染色体HXT6 HXT6/7 HXT7扩增的细胞所取代，表明环状 DNA 是染色体扩增的中间体。总之，环状DNA的异质性提供了适应的灵活性，但这种异质性随着年龄的增长而显着减弱。